MARCH1 (MARCHF1; RNF171) of 189 aas and 2 TMSs near, but not at, the C-terninus. It is an E3 ubiquitin-protein ligase that mediates ubiquitination of the transferrin recpeotor (TFRC), CD86, FAS and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies (Lapaque et al. 2009). By constitutively ubiquitinating MHC class II proteins in immature dendritic cells, it down-regulates their cell surface localizations, thus sequestering them in the intracellular endosomal system (De Gassart et al. 2008). It, and its orthologs, play roles in antiviral innate immunity (Zheng 2021) (see family description).

MARCH1 of Homo sapiens

MIR2 (K5) of human herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's sarcoma-associated herpesvirus). E3 ubiquitin-protein ligase promotes ubiquitination and subsequent degradation of host MHC-I, CD86, ICAM1 and CD1D molecules, to prevent lysis of infected cells by cytotoxic T-lymphocytes and NK cell. It binds target molecules through transmembrane interactions. Different features of CD86 to downregulate surface expression are responsible for binding (Trenker et al. 2021).

MIR2 of Herpies viruses

The E3 ubiquitin-protein ligase of 910 aas and 15 TMSs in a 3 + 6 + 6 TMS arrangement.  The last two 6 TMS units are probably duplicates of each other.  The ligase promotes 'Lys-48'-linked ubiquitination of target proteins, leading to their proteasomal degradation (Hassink et al. 2005).

E3 ubiquitin:protein liganse of Homo sapiens

MARCH6 of 910 aas and ~15 TMSs in a 3 + 6 + 6 TMS arrangement. It is a E3 ubiquitin-protein ligase that promotes 'Lys-48'-linked ubiquitination of target proteins, leading to their proteasomal degradation (Hassink et al. 2005). It promotes ubiquitination of DIO2, leading to its degradation (Zavacki et al. 2009) as well as of SQLE, leading to its degradation (Zelcer et al. 2014). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. It may cooperate with UBE2G1 (Hassink et al. 2005). Some members of TC family 3.A.16 (i.e., 3.A.16.1.2 and 1.5) utilize homologues as part of a multicomponent system.  Doa10/MARCH6 architecture interconnects E3 ligase activity with lipid-binding transmembrane channel to regulate SQLE (Botsch et al. 2024).

MARCH6 of Homo sapiens

MARCH2 (MARCHII) of 246 aas and 2 TMSs, near the C-terminus of the protein. It is an E3 ubiquitin-protein ligase that may mediate ubiquitination of TFRC and CD86, and promote their subsequent endocytosis and sorting to lysosomes via multivesicular bodies (Nakamura et al. 2005). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates and may be involved in endosomal trafficking through interaction with STX6 (Bartee et al. 2004).

MARCH2 of Homo sapiens

RING finger membrane protein of 1631 aas and 18 TMSs in an apparent 3 + 3 + 5 + 6 TMS arrangement.

RING finger protein of Aspergillus sclerotialis

Uncharacterized protein of 423 aas and 4 C-terminal TMSs.

UP of Gossypium mustelinum

Uncharacterized protein of 629 aas and 3 C-terminal TMSs.

UP of Podila horticola

Uncharacterized protein of 265 aas and 2 C-terminal TMSs.

UP of Drosophila pseudoobscura

MARCH3, RNF173, MARCHF3, of 253 aas and 2 TMSs, close to each other and near the C-terminus of the protein.

MARCH3 of Homo sapiens

Uncharacterized protein of 1102 aas and up to 11 TMSs, possibly in a 5 + 6 TMS arrangement.

UP of Leishmania guyanensis

E3 ubiquitin-protein ligase, MARCH7 isoform X5, of 862 aas and possibly 3 C-terminal TMSs.

Protein liganse of Petromyzon marinus (sea lamprey)

Uncharacterized protein of 260 aas and 2 TMSs (C-terminal).

UP of Citrus sinensis

E3 ubiquitin-protein ligase MARCH2 of 207 aas and 2 C-terminal TMSs.

MARCH2 of Zea mays